Demineralized bone matrix (DBM) refers to a bone whose minerals have been removed by adding it to an acid. Demineralized bone matrix mostly consists of highly cross-linked collagen and comprises the remaining non-collagenic proteins such as TGF-β, PDGF, osteopontin, osteonectin, bone morphogenetic protein (BMP) and the like.
When the demineralized bone matrix was incorporated (filled) into a mouse muscle, an ectopic bone formation was observed in the incorporated site. This experiment proved that in order for a bone to grow, a material that can induce undifferentiated cells among a group of bone-forming cells to be differentiated should exist in the bone matrix. BMP is such a protein substance existing in the bone matrix (Urist, M R, Strates, B S, bone morphogenetic protein, J. Dental Res. 50:1392-1406, 1971). BMP can be separated from the bone or prepared through the recombinant gene technique.
BMP is a group of proteins that belong to the TGF-β superfamily and was classified based on its ability to induce bone formation (Wozney, J M, Science 242:1528-1534, 1988). The BMP family can be classified into BMPs such as BMP-2 and BMP-4; osteogenetic proteins (OPs) such as OP-1 (or BMP-7), OP-2 (or BMP-8), BMP-5, BMP-6 and Vgr-1; cartilage-derived morphogenetic proteins (CDMPs) such as CDMP-1, BMP-14 and GDF-5; growth/differentiation factors (GDFs) such as GDF-1, GDF-3, GDF-8, GDF-11, GDF-12 and GDF-14; and a subfamily such as BMP-3, osteogenin, BMP-9, GDF-2 and BMP-10.
Various compositions have been used for healing damaged bone tissue. They can act as a framework to support new bone growth and provide growth factors for new bone-growth induction. U.S. Pat. No. 4,394,370 to Jefferies disclosed a tissue-healing composition comprising a recombinant collagen, a demineralized bone matrix and BMP. U.S. Pat. No. 4,440,750 to Glowacki et al. disclosed a hydrating composition consisting of a recombinant collagen and a demineralized bone matrix.
However, the bone-repair efficacy of these compositions is low because the bone growth factors are not released in the early stage but trapped within the highly cross-linked collagen network of the demineralized bone matrix and slowly released as collagen components degrade. As an alternative to such a slow release, a method for separating the bone growth factors from the demineralized bone matrix was suggested (U.S. Pat. No. 7,132,110). However, a number of steps such as extraction, purification, mixing with a dispersion solvent or combination with another carrier are required for such a separation. In addition, it has the disadvantage of causing damage to the bone growth factors and collagen during the separation process.
Furthermore, when the demineralized bone matrix in a powder state is used alone, it is impossible to inject and difficult to maintain and modify the shape; thus, handling is problematic. Thus, in order to provide better injectability, and shape-maintenance and modification properties, a connection with other substances has been raised. Up to now, combination products with an organic polymer such as gellatin, glycerol, poloxamer and hyaluronic acid have been reported, but they did not satisfy all of injectability, shape-maintenance (handling), content and biocompatibility.
Thus, there is an ever-increasing need to develop a bone-repair composition that can release the bone growth factors in the early stage, can be harmless to the human body and can improve injectability and shape-maintenance (handling) of the demineralized bone matrix.